A scalable protocol for the radiosynthesis of clinical grade lutetium-177-labeled theranostic agents
Journal Title
Nature Protocols
Publication Type
Online publication before print
Abstract
Theranostics utilizes tandem targeted diagnostic and therapeutic agents that are molecularly analogous. In a theranostic approach, the diagnostic agent is a tracer typically radiolabeled with a positron emission tomography radionuclide such as fluorine-18 or gallium-68. Utilizing the selectivity of the tracer, the therapeutic agent is subsequently radiolabeled with an ablative radionuclide such as the β(-) emitting lanthanide lutetium-177 ((177)Lu). (177)Lu is typically incorporated into theranostics using the chelators 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) and 2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)pentanedioic acid (DOTAGA) that are used to prepare the (177)Lu-radiopharmaceutical [(177)Lu]Lu-DOTA-TATE, [(177)Lu]Lu-PSMA-617 and [(177)Lu]Lu-PSMA-I&T. Here we describe the scalable and validated production for these (177)Lu-radiopharmaceuticals and further include the necessary quality control protocols. The procedures can be generalized and support both carrier added and noncarrier added (177)Lu sources for use in a clinical setting. With robust procedures that accommodate (177)Lu activity levels from 5 to 100 GBq, the procedures ensure stability for up to 8 h postproduction and achieve an average activity yield of 98%. As proven in over 1,000 patient cycles, this methodology is adaptable to both centralized production facilities and regional centers, enabling versatile application across small and large-scale production settings.
Department(s)
Cancer Imaging
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